title: The Trypanosoma brucei gambiense secretome impairs lipopolysaccharide-induced maturation, cytokine production, and allostimulatory capacity of dendritic cells.
abstract: Trypanosoma brucei gambiense, a parasitic protozoan belonging to kinetoplastids, is the main etiological agent of human African trypanosomiasis (HAT), or sleeping sickness. One major characteristic of this disease is the dysregulation of the host immune system. The present study demonstrates that the secretome (excreted-secreted proteins) of T. b. gambiense impairs the lipopolysaccharide (LPS)-induced maturation of murine dendritic cells (DCs). The upregulation of major histocompatibility complex class II, CD40, CD80, and CD86 molecules, as well as the secretion of cytokines such as tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-6, which are normally released at high levels by LPS-stimulated DCs, is significantly reduced when these cells are cultured in the presence of the T. b. gambiense secretome. Moreover, the inhibition of DC maturation results in the loss of their allostimulatory capacity, leading to a dramatic decrease in Th1/Th2 cytokine production by cocultured lymphocytes. These results provide new insights into a novel efficient immunosuppressive mechanism directly involving the alteration of DC function which might be used by T. b. gambiense to interfere with the host immune responses in HAT and promote the infectious process.
authors.affiliation: UMR 177, IRD-CIRAD, Montpellier, France.
authors.forename: Edwin
authors.initials: E
authors.lastname: Garzón
authors.forename: Philippe
authors.initials: P
authors.lastname: Holzmuller
authors.forename: Rachel
authors.initials: R
authors.lastname: Bras-Gonçalves
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.forename: Gérard
authors.initials: G
authors.lastname: Cuny
authors.forename: Jean Loup
authors.initials: JL
authors.lastname: Lemesre
authors.forename: Anne
authors.initials: A
authors.lastname: Geiger
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D040081:Protein Array Analysis / Q000379:methods; D017208:Rats, Wistar; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014347:Trypanosoma brucei gambiense / Q000235:genetics / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10